This research will be done primarily in Kenya at the Kenya Medical Research Institute (KEMRI) in Mwea and Nairobi, in collaboration with Dr. Gerald Mkoji, as an extension of NIH application R01 AI044913 entitled "Evo-epidemiology of Schistosoma mansoni in western Kenya" for which Eric S. Loker, University of New Mexico, serves as PI. The parent grant has as one of its primary aims the development of robust new microsatellite-based techniques for revealing the biology of schistosomes in the human host, and focuses particularly on adult human subjects and foci of transmission along the shores of Lake Victoria. Building on the techniques developed in the parent grant, we will complement and expand its impact by applying these techniques to a population of schoolchildren in Mwea who are enrolled in a study directed by Dr. Charles Mwandawiro of the Eastern and Southern Africa Centre of International Parasite Control (ESACIPAC) which was established at KEMRI in 2001 with the support of the Japanese Government, through the Japan International Cooperation Agency (JICA). Transmission of S. mansoni in Mwea is stream-based and is thus representative of the setting in which this parasite exists in much of sub-Saharan Africa. Using multiplex PCR amplification of 13 microsatellite loci from individual S. mansoni miracidia obtained from fecal samples from ~23 infected children, we will test fundamental hypotheses relating to schistosome biology in the human host. We will test whether S. mansoni genetic diversity (as assessed by measures of allelic richness) increases with subject age (aged 6 to 14) and infection intensity (ranging from 1 to >400 eggs/gram of feces), and whether worm populations exhibit signs of clonality as a result of restricted opportunities for infection. The extent to which S. mansoni populations are genetically differentiated among each child and among children from a particular village or school will also be determined. Each child to be studied will be treated with praziquantel as part of the umbrella JICA project, and we will assess the impact of treatment on the genetic composition of the S. mansoni populations they harbor. Furthermore, the design of the JICA project allows for retreatment of children should they become reinfected as expected, so we will also monitor miracidial genotypes following one and possibly more re-treatments. As similar treatment programs targeting children are widespread in Africa now, it is imperative that we develop these approaches as powerful ways to monitor the efficacy of the control programs and the possible emergence of resistance. This FIRCA proposal will also allow us to make insightful comparisons with the results of the parent grant involving human subjects of different age and living in fundamentally different circumstances of transmission. PUBLIC HEALTH RELEVANCE: Schistosomiasis is a neglected parasitic disease that infects an estimated 200 million people world wide with many suffering from severe morbidity due to this disease (Crompton, 1999;Chitsulo et al. 2000). At present, the only widely endorsed means for controlling schistosomiasis is treatment with praziquantel (PZQ). Given the current one dimensional approach to control, we need to better monitor changes in the biology of the worms and our efforts to control them. This will only be possible with a more detailed understanding of the evolutionary history and population biology of S. mansoni. Using novel techniques, our proposed research will characterize schistosome populations within humans in terms of genetic diversity, genetic structuring, and presence of clonal genotypes as well as monitor the recruitment process of new worms and the evolution of drug resistance. This information will be valuable for understanding transmission dynamics, spread of novel traits such as drug resistance, and population dynamics of schistosomes.